The energy metabolism of cardiac muscle is coupled to functional demands so that myocardium mobilizes just enough energy to satisfy the work demand. The control mechanisms involved in the regulation of metabolism which bring about the necessary energy production are not clear. It is the purpose of this investigation to elucidate the mechanisms involved in the regulation of energy metabolism which permit the necessary energy production during various levels of myocardial activity. Cellular energy metabolism with particular emphasis on the controls of energy production will be studied in rat myocardial cells in monolayer cultures, as a model system. Adenylate charge, phosphorylation state, phosphorylcreatine mol fraction and the enzyme creatine kinase will be determined; rate of oxygen utilization will be measured. The cell cultures will be subjected to normal physiologic conditions and to perturbations of energy metabolism e.g., hypoxia, adriamycin cardiotoxicity. This investigation could pave the way to a better understanding of the mechanism of decreased mechanical performance of the myocardium under conditions of metabolic disturbances and to appropriate interventions.